Human Physiology
Physiology 7 Student Notes 1
First Session
Instructor: Dean Sheehy, MEd, CLS, WTII
Take Roll
Review Syllabus
Grading for lecture.
Grading for lab. No lab reports graded, only exams!
Prerequisites: Human Anatomy, Chemistry
Purpose for taking class.
How to succeed in Physiology.
Time: 3 hours per lecture hour, 3 hours for lab per week.
Demonstrated success in prerequisites.
Family support.
Read material.
Learn as you go. Develop a foundation. Enjoy the subject.
Anoint your notes from text, review with others
immediately following class sessions.
Get to know others. Study together.
Attend regularly. Be on time.
Make use of instructor. I want all of you to do well.
Introduction to Human Physiology
The Scope Of Physiology
Chapter 1
Definition physiology = the study of how living things function. The
functions of body systems and the basis of how they work.
Present day view is that all physiological processes can be explained
according to the laws of chemistry and physics. Physiology draws on
these fields to explain body functions.
No supernatural forces or unexplained forces are considered.
Physiology 7
PhysiologyStudentsNotes1
1
The Basic Unit of Function of All Organisms = Cell
Characteristics of Living Cells (Life Processes) p. 7-8
Cells exhibit certain activities that can be considered the
criteria of life.
1. Intake of Materials
For energy to power cellular activities or,
Materials synthesis.
Origin: from breakdown products of food.
2. Output of Materials
The elimination of wastes of metabolism.
3. Metabolism
All chemical reactions in the body.
Metabolic reactions are of 2 basic types:
1. Anabolism: Metabolic processes that involve the
building up or synthesis of complex (organic)
molecules . This process requires energy.
Example of anabolism: Taking in food and storing it.
2. Catabolism
The opposite of anabolism. Metabolic reaction in which
complex molecules are broken down into simpler ones.
This process yields energy.
Example of catabolism: Breakdown of obtained or stored
foods for energy.
4. Reproduction: 2 types:
1. Replacement of worn out and damaged cells. Somatic
cells. Duplicates of existing cells.
2. The production of a new individual. Germ line cells
(gametes). New combinations of genetic traits.
Physiology 7
PhysiologyStudentsNotes1
2
5. Growth: increase in size that results from 2 ways:
1. Growth of an individual cell.
2. Increase in number of cells.
6. Movement:
Occurs within cells, entire cell can move, organs can move, or
the whole organism can move.
7. Responsiveness
Cells respond to changes in the internal or external
environment. Homeostasis.
Since the body is made up of cells, the body exhibits these
properties as a whole.
Levels of Structural Organization in the Human Body
figure 1.1 page 3
Chemical level: atoms, molecules, ions
Cellular level: the basic unit of life
In our bodies there are about 40 trillion cells.
The cells are organized into tissues.
Tissue level
Tissues = groups of cells that work together to perform a
similar function.
4 Elementary Tissues in the Human Body. page 4, 104
1. Epithelial Tissues = Function to cover the body and
line its structures, forms glands. E.g. skin stratified
squamous
2. Connective Tissues = Connecting and support,
store energy, immunity. E.g. areolar C.T. just deep to
the epidermis
3. Muscular Tissue = Contractile tissue causes
movement. E.g. skeletal, cardiac, smooth
Physiology 7
PhysiologyStudentsNotes1
3
4. Nervous Tissue = Detect change, conduction of
impulses. E.g. CNS and peripheral nerves
Organ Level
2 or more tissues that are organized for a specific function
= Organ. Ex: stomach, heart, liver, kidney
System level
System = 2 or more related organs that are coordinated to
perform a specific function. Ex: digestive system
Organismal level
Organism- one living individual. All systems functioning
together to create a living human.
Homeostasis: homeo = sameness, statis = standing still
When systems work properly, they maintain the organism
in an optimal state.
Homeostasis: Maintaining physiological limits at a set
point. The maintenance of this state = homeostasis. Same
state or steady state.
Homeostatic imbalance will cause disease or death. Ex:
blood glucose, RBC level, blood pH.
Constant adjustments are made to maintain the steady
state.
Are you are aware of your body's homeostatic attempts?
When you are hungry or hot, you become irritable or less
efficient. So, you eat and sweat respectively.
Aging brings on aging and death of cells = slow drifting
away from optimal condition of life. In other words, aging
can be looked upon as a failure to maintain homeostasis.
Feedback Systems (Loops) to control homeostatis
figure 1.2 p. 9
Physiology 7
PhysiologyStudentsNotes1
4
A feedback system involves a cycle of events where the status
of a condition is continually monitored and fed back to a central
control.
Components of feedback loop:
1. Stimulus- change in environment that is sensed by:
2. Receptors- these sense changes and sends information
to:
3. Control center- receives the input and provides output
to:
4. Effectors- these bring about a change to return to
homeostasis
Negative feedback system- the system that reverses the original
stimulus. Most systems use this type. Used to maintain
constant set points over long periods of time.
Example: Homeostasis of blood pressure. Set point: Keep
blood pressure about 120/80.
If low, constrict arterioles to create more resistance, drink fluids
to increase blood volume, slow heart rate, etc.
If too high, decrease heart rate. see fig 1.3 p. 10
Positive feedback system- The response enhances or
intensifies the original stimulus until stimulus is removed.
Rarely used in human physiology.
Example: Fig 1.4 p11 Homeostasis of labor contractions
(oxytocin stimulates more uterus contraction). Want more and
stronger contractions until birth occurs (the baby leaves and
quits stretching the uterus that removes the stimulus).
Physiology 7
PhysiologyStudentsNotes1
5
Systems of the Human Body
see table 1.2 page 4-6.
An introductory review of the 11 body systems.
Body systems work together to bring about homeostasis.
There are 2 Controlling Systems: Monitor and detect changes in
body components.
1. Nervous System- Components: brain, spinal cord, nerves,
and sense organs.
Functions: regulate body activity through nerve impulses.
Consciousness, awareness.
2. Endocrine System- Components: All glands that produce
hormones.
Function: regulates body activity through hormones in the
blood.
Both serve to coordinate all other body functions.
Vegetative Systems: Provide nutrition for cells and removal of
wastes. Vegetative refers to a passive process.
1. Digestive System- Components: long tube with associated
organs (gallbladder, liver, pancreas)
Function: breakdown food mechanically and chemically,
and elimination of solid waste.
2. Respiratory System- Components: Lungs and tubes leading
to exterior environment.
Function: supplies 02, eliminates CO2, and regulates acidbase balance of body (with kidneys).
3. Urinary System- Components: organs that produce and
eliminate urine.
Physiology 7
PhysiologyStudentsNotes1
6
Function: eliminate metabolic wastes, regulate water
balance, and maintains acid-base balance (with respiratory
system).
4. Cardiovascular System- Components: Blood, heart, and
blood vessels.
Function: Transportation.
Distributes nutrients to cells (02, glucose), eliminates waste
from cells (CO2, ammonia, lactic acid).
Maintains acid-base balance, protects against disease
(non specific immunity), prevents hemorrhage by forming
clots, regulates body temperature.
Protective Systems: Provide protection for the organism and its
parts.
1. Integumentary (Skin) System- Components: skin and
derivatives (hair, nails, sweat and oil glands).
Function: mechanical protection, regulate body
temperature, eliminates wastes.
2. Lymphatic and Immune System- components: lymph,
lymphatic vessels, lymph nodes, spleen. Lymphatic tissues
contain large numbers of white cells called lymphocytes.
Function: protects body by filtering blood and production of
proteins called antibodies and immune cells.
3. Cardiovascular System: blood also has cells that protect the
body: phagocytes and neutrophils.
Other Systems
1. Skeletal System- Components: bones and joints of the body.
Physiology 7
PhysiologyStudentsNotes1
7
Function: protects and supports the body. Assists in body
movements. Stores minerals.
2. Muscular System- Components: primarily skeletal muscle
tissue which is attached to bones, also smooth and cardiac
muscle.
Function: Powers movements of the body and stabilize his
body positions. Generates heat.
3. Reproductive System- Components: organs (testes and
ovaries) that produce reproductive cells (gametes), and other
organs that deliver and store reproductive cells.
Function: Reproduce the species over time.
This brief review of the body systems helps demonstrate the
dependence of the various systems on each other for functioning of
the entire organism to maintain homeostasis.
Physiology 7
PhysiologyStudentsNotes1
8
Basis of Cell Structure and Function Chapter 3 p 60
Introduction
The cell is the basic unit of function in humans. They are smaller
than can be seen without a microscope so its hard to relate to cells
as life.
The 7 characteristics of living cells or what living cells do are:
Intake, metabolism (anabolism and catabolism), output
(elimination of wastes), reproduction, movement, growth,
responsiveness.
Although each of your 100 trillion cells exhibit each of these
characteristics that does not mean that all of your cells are exactly
the same. In multicellular organisms we tend to see a division of
labor, or specialization, amongst the cells.
That is, the different cells within the body perform different jobs or
functions. Ex: muscle cells and nerve cells.
Fig 3.1 p 60
Due to the differences in function of the cells we can see great
diversity in cell:
1. Size
2. Shape Of Cells
Cell Size
Cells vary in size from the smallest bacteria (1 micrometer) to the
largest cell, an ostrich egg.
There are certain limits that are placed on cell size. They cannot be
infinitely large or infinitely small. Information must pass from cell
membrane to nucleus in a timely way for responses to be relevant.
Human cells mostly between 7-30um across. However, RBCs are
about 7 um where a nerve cell can be a meter long.
Physiology 7
PhysiologyStudentsNotes1
9
Limits To Cell Size
1. A cell must be at least large enough to contain the
macromolecules (proteins and nucleic acids and their products) and
organelles necessary to sustain life.
2. The upper size limit of cells depends on 2 things:
a. Ability of the nucleus (eukaryotes) to control what takes place in the
cytoplasm.
Cells can sometime get around this by fudging a bit. If the
cytoplasm is very large, you may find multinucleated cells (muscle
cells).
b. The extent to which nutrients and waste products can efficiently pass
through the cytoplasm. The greater distance involved, the much greater
the time involved in moving from one place to another.
Differences in the shape of cells are obvious. Some discussion on p. 107-8
The shape of cells depends on function.
Examples:
1. Cells that absorb things typically have microvilli. These
increase the amount of absorptive or secretory area
significantly without increasing the amount of cytoplasm.
2. Shape of RBC (erythrocytes), a biconcave disk, allows
maximum surface area for rapid diffusion of 02 and CO2. No
nucleus, just a sack of macromolecules, so very flexible for
passage through capillaries.
3. Thin for allowing passage of materials. Squamous
pulmonary epithelium of alveoli allows for diffusion of gasses
to adjacent capillary endothelium.
Physiology 7
PhysiologyStudentsNotes1
10
Movement of Materials Across Plasma Membranes
How do cells acquire the materials necessary for activity?
Things may move into cells by passive processes that do not require
energy use by the cell:
see table 3.1 page 74.
1.
2.
3.
4.
Diffusion.
Osmosis.
Bulk flow.
Facilitated diffusion.
Or, they may move into the cell by active processes that require
energy used by the cell:
1. Active transport.
2. Vesicular transport.
a. Endocytosis
1. Pinocytosis.
2. Phagocytosis.
3. Receptor mediated endocytosis. Example: viral receptors.
b. Exocytosis.
Passive Processes
Movement of molecules due to differences in concentration gradient
or pressure.
No energy is expended by the cell.
Molecules are always in motion (random) using kinetic energy obtained
from their surroundings.
4 types of passive processes:
1. Diffusion (simple diffusion)- movement of molecules from an area
of high concentration to an area of low concentration. See fig. 3.6 p.65
Example: Smoking cigarette in a room. Smoke will first be concentrated
around smoking person in room. Slowly the smoke moves away from
the concentrated source (to our dismay) until the molecules become
Physiology 7
PhysiologyStudentsNotes1
11
equally distributed in the room at which time they are said to be in
equilibrium. This called second hand smoke.
Have the molecules stopped moving? No. There are just as many
molecules moving in one direction as another but no net movement.
This called Dynamic equilibrium.
Rate of Diffusion p. 65-6
Rate of diffusion will be influenced by:
1. Temperature: increase temperature, increase kinetic energy, increase
rate of diffusion.
2. Concentration gradient (difference): increase gradient, increase
diffusion. The rate of diffusion will slow as equilibrium is approached,
or said another way the gradient decreases.
3. Size of diffusing molecule- increase size (molecular weight and radius
of molecule), decrease diffusion. More friction with solvent.
Where does diffusion take place in the human body?
Anywhere solute is dissolved in solution (water based solvent in
physiologic systems).
a. Selective movement across a lipid membrane permeable to:
H20, small non polar uncharged molecules, fat soluble.
Ex: H2O, O2, CO2, N2, steroids, fat sol vitamins, small alcohols,
ammonia.
Ex: Passage of gases at lung surface (CO2, O2).
Note: impermeable to ions and polar molecules. Water in an
exception.
b. Selective movement across a membrane within a specialized
transmembrane protein channel permeable to: small to
medium polar and charged substances.
Ex: Facilitated diffusion of glucose molecule, a polar molecule
Note: larger molecules such as proteins are too large to diffuse
through a membrane.
Physiology 7
PhysiologyStudentsNotes1
12
2. Osmosis- Is a specialized type of diffusion. Fig. 3.7 p.66
Osmosis is the movement of water (through a selectively permeable
membrane) from an area of higher water concentration to an area of
lower concentration.
In the case of osmosis, selectively permeable means the membrane will
allow the passage of water molecules but not solutes. These solutes are
general charged (electrolytes: Na+, Cl-) or polar (glucose).
The selectively permeable membranes in our experiments mimic the
phospholipid cell membranes of animal cells.
Examples of osmosis in the body:
a. Kidney urine formation. Osmotic gradient established in
nephron so water and salts can be selectively retained or
removed.
b. Movement of interstitial fluid back into capillaries after
forced out by bulk flow of arterial pressure.
c. Movement of water through the walls of the digestive
tract as solutes are absorbed.
Remember: Body compartments, and cells and interstitial spaces are
separated from each other by selectively permeable membranes.
If osmotic balance gets disturbed, water will move to rebalance the
concentration gradient. The results can be hazardous to the cell!
Example:
Question: How do you wash red blood cells? Distilled water? No, use a
saline solution.
Tonicity and red blood cells. See figure 3.8 page 67
Isotonic saline = 0.9% NaCl.
Isotonic saline has the same solute concentration as the cell
contents of a red cell. Cell cytoplasm = 0.9% solutes and 99.1%
water
Physiology 7
PhysiologyStudentsNotes1
13
Hypotonic saline or distilled water will cause the red cells to swell or
burst.
Hypotonic solution means there is less solute outside than inside the
red cell.
Hypertonic solution will cause the red cell to shrink and become
crenated.
Hypertonic means the solution has more solutes outside than the
inside of the red cell.
Example: Severe malnutrition in the human leads to loss of protein in the
body and the blood plasma. The blood plasma has less solute so
becomes hypotonic (less ability to pull water). Interstitial fluid water does
not move back into the venules as it should, and can cause bloating and
a large abdomen.
Think of the body as a series of compartments separated by
membranes. If osmotic balance is off, fluid will move to one side or the
other to balance the pressure. ECF (extra cellular fluid found in interstitial
space and vascular space) versus ICF (intracellular fluid inside of cells).
These concepts are important in successful IV therapy.
3. Bulk Flow: the movement in the same direction of large numbers
of solute particles in solution due to differences in water or air
pressure. Forces move particles in unison, not random motion.
Example: Filtration- of materials through a permeable
membrane, due to pressure.
Example:
a. Passage of materials through capillary walls due to blood
pressure.
b. Non-selective filtration that occurs in the nephron.
c. Movement of air in and out of lungs due to changes in air
pressure by lung expansion and contraction.
4.Facilitated diffusion Fig. 3.10 page 69
Solutes (ions, glucose, urea, some vitamins) move down a
concentration gradient from a region of higher concentration to a
Physiology 7
PhysiologyStudentsNotes1
14
region of lower concentration with the help of specific integral
proteins in the phospholipid bilayer cell membrane. These are under
genetic control.
These serve as water filled channels or transporters (carriers)
for specific substances.
These substances maybe too lipid insoluble to diffuse through
the plasma membrane.
Example: Glucose is moved across the plasma membrane by a
transporter protein.
The glucose is phosphorylated as it moves into the cell and keeps
the intracellular concentration of glucose very low to favor the
concentration gradient.
Insulin can accelerate the facilitated diffusion by promoting the
insertion of transporter proteins and thus helps to achieve
homeostasis by moving glucose into cells quickly.
Active Processes for transmembrane transport
Active Transport: The movement of molecules across a cell
membrane from an area of lower concentration to an area of higher
concentration, requiring energy expenditure by the cell.
Opposite of osmosis. Fig 3.11 p 70
Energy is usually in the form of ATP that is used to change the shape of
a transport protein in the plasma membrane. Fig 2.25 p 54
About 40% of the ATP generated in a cell is used for active transport.
70% in neuron.
This involves moving things against a concentration gradient. So
they are often called pumps.
Example substances: Na+, K+, H+, Ca2+, Cl-, amino acids.
Example of active transport: Na+/K+/ATPase pump. Fig. 3.11, page 70
a. This pump expels Na+ (3) from cells and brings K+ (2) inside.
Physiology 7
PhysiologyStudentsNotes1
15
The pump maintains a low concentration of Na+ in the
cytoplasm by pumping it out against the concentration
gradient.
b.The K+ moves into cells against its concentration gradient.
All cells have hundreds of Na/K pumps in each square
micrometer of membrane surface.
This pump must work continually because K+ and Na+ slowly
leak across the plasma membrane through leakage channels
down their concentration gradients.
These pumps help provide the gradients necessary for muscle
contractions and nerve impulse transmission to occur.
Drugs or poisons can affect the active transport mechanism.
Example: Cyanide is lethal because it can shutdown active transport in
cells throughout the body. Effects metal containing enzymes, esp.
cytochrome oxidase and enzyme used in mitochondrial respiration to
make ATP.
Example: p. 71 Digitalis slows the membrane boung sodium pump as it
binds to Na+K+ ATPase in cardiac myocytes so sodium accumulates in
the cell. This causes more Ca2+ to stay in cell and results in a stronger
heartbeat.
The slower heartbeat allows time for more ventricular filling and blood
ejection. Useful for congestive heart failure treatment or used on poison
darts by native peoples.
The point: Ion balance inside and outside cell is crucial to normal
functioning of nerve and heart cells, especially K+.
We won’t discuss symport (2 substances move in same direction) and antiport (2
substances move in opposite directions) activities of cellular membrane transport.
Vesicular Transport- large molecules cannot move directly across
the cell membrane and must be transported in bulk processes.
We will discuss:
Physiology 7
PhysiologyStudentsNotes1
16
3 types of vesicular transport that bring materials into the cell, and,
1 type that moves materials outside the cell.
Endocytosis- processes that brings substances into cells using a
segment of the plasma membrane to surround and enclose the
substance to be taken in the cell.
3 types will be discussed:
1. Phagocytosis- "cell eating". Fig. 3.14 page 73
Solid particles are surrounded by projections of the plasma
membrane (pseudopods) and become enclosed within a sac of
membrane (phagocytic vesicle) that moves into the cell.
The solid material is digested by enzymes provided by
lysosomes.
Example: Phagocytes (neutrophils, macrophages) are cells present
in most tissues that destroy bacteria and other foreign substances.
Crawl around doing surveillance or signaled to aggregate at sites
of infection or cellular damage.
2. Pinocytosis- "cell drinking". Fig 3.15 p 73
Engulfed material (ECF and molecules) is a tiny droplet of
extracellular fluid that becomes surrounded by cell membrane
as it folds inward forming a pinocytic vesicle.
Ex: Used to degrade macromolecules to amino acids for cell
growth.
3. Receptor-mediated endocytosis Fig. 3.13 page 72
Specific molecules or particles can bind to specific proteins
receptors in the plasma membrane.
Examples:
a. Needed substances such as cholesterol, iron, and
vitamins can be transported this way.
Ex: Inherited lack of protein receptor = familial
hypercholesterolemia. Cholesterol accumulates in blood,
increasing coronary artery disease risk.
Physiology 7
PhysiologyStudentsNotes1
17
b. Hormones can deliver messages to target cells to perform
a specific response.
Ex. insulin
b. Viruses enter cells by this mechanism.
Ex: HIV (human immunodeficiency virus) enters human cells
by binding to the receptor called CD4 found on helper T cells.
Exocytosis Fig. 3.22 page 80
The process that brings substances from inside the cell to the cell
membrane where they are released to the outside.
Membrane enclosed structures called secretory vesicles form inside
the cell (golgi apparatus) and fuse with the plasma membrane.
This process occurs in most cells.
Example:
1. Nerve cells: release neurotransmitters to influence another neuron or
muscle cell.
3. Secretory cells: digestive enzymes released to the GI tract and protein
hormones (insulin) are released to the blood stream.
Cell Structure and Function
fig. 3.1 p.60
Two structures are apparent to us when we view cells with our
microscope in the lab are:
Nucleus- Directs the cellular activity through genetic expression.
Cytoplasm- Substance or matrix between cell membrane and
nucleus.
It contains many small factories type structures. These are
called cell organelles and are responsible for synthesis,
metabolism, and packaging of materials.
We will discuss a number of these organelles.
Cell Membrane or Plasma Membrane
Physiology 7
PhysiologyStudentsNotes1
18
The cell’s outer membrane limits the boundaries of cell, separating
its contents from internal fluids of the body. The membrane must
stay intact for its survival.
We will find this is not the only membrane found in a cell. There are
several others found in internal structures.
The membrane systems serve to compartmentalize the various
organelles and their functions within a cell.
Membrane Systems fig. 3.2 p 61
All membranes are composed of 2 major components:
1. Lipids
2. Protein
All membranes however are not alike; they vary the proportion (ratio)
of lipid and protein.
Let's take a look at how the 2 components of a membrane (lipids,
protein) are arranged with each other to form a membrane.
Construction of a Membrane
A lipid (phospholipid) could be diagrammed as follows:
figure 2.18, p. 47
There are 2 major components:
1. The head is composed of a phosphate group linked to a
small charged group that is hydrophilic ("water loving").
It occupies the 3rd position of the glycerol backbone of a
triglyceride.
2. Fatty acid tail: the 2 fatty acids that make up the tail have no
polar charge and are hydrophobic ("water fearing").
Lipids take on the following arrangement in the membrane:
fig. 2.18 p47
Physiology 7
PhysiologyStudentsNotes1
19
Notice the hydrophobic tails pointing inward towards each other
inside the membrane and hydrophilic heads pointing outward facing
the interstitial and the intracellular areas.
We can see from this arrangement that molecules not soluble in
lipids will have a hard time getting through the lipid portion of the
membrane. This creates a barrier to diffusion of most substances,
especially those that are polar or charged.
Membrane Proteins
How do such polar molecules such as glucose (not soluble in lipids)
get in? Or through membrane?
Protein subunits "float in a sea of lipids" within the membrane.
See figure 3.2 p. 61
Notice how the phospholipid bilayer membrane is embedded with
many different proteins. These are generally not in a fixed position
but can move in a fluid motion with the lipids. Some proteins extend
from cytoplasm to extra cellular space while other are more in or
outside the membrane.
Functions of membrane proteins
fig. 3.3 p.63
Fig 3.3 part 5
1. Cell identity markers
Some proteins are antigens that serve as self recognition cell
markers (or cell identity markers). Tissue transplant antigens, blood
types, immune functions, species barriers, etc.
Example: each person has their own specific antigens (major
histocompatibility (MHC) antigens) that its body's immune system will
recognize as being "self".
In transplants from other people, rejection reactions happen because of
the different ‘self’ antigens on the donor cell surface.
Foreign antigens stimulate an immune response (a cellular or antibody
attack) in the recipient to combat the foreign material.
Physiology 7
PhysiologyStudentsNotes1
20
ABO and Rh blood groups are based on the presence of absence of
membrane proteins.
Fig. 3.3 Part 1&2
2. Control Passage of Substances
Some proteins (transporters or ion channels) can act as transport
devices, helping molecules to get into the cells.
Most membranes are selective: they let some things through and not
others.
Factors That Determine Membrane Selectivity other than
proteins:
a. Thickness of Membrane- simply a greater distance to
cover. E.g. diabetes, CF
b. Size of Substance Attempting to Penetrate- a few small,
uncharged,non polar molecules (oxygen, CO2) and a few
small polar (for example, water and urea) can pass
through the phospholipid bilayer.
Pore size (7-8 angstroms) in a channel determines
what will penetrate.
Glycerol, ethyl alcohol are near the upper size limit for
pore passage.
c. Lipid Solubility- membrane contains much lipid.
The more lipid soluble (nonpolar, hydrophobic) a molecule
is, the easier it will travel through the membrane.
Ex:
1. Lipid soluble antibiotics can enter CNS.
2. Lipid soluble hormones go straight to nucleus to
influence cell activities.
d. Electrical Charge on membrane in comparison to
charge on molecule and ions.
Like charges repel, opposites attract. Fig 3.4, p. 64
Physiology 7
PhysiologyStudentsNotes1
21
Most cell membrane membranes have a negative
potential inside and relative positive outside.
This aids inflow of positive ions (cations), and hinders
the inflow of negative ions (anions). This electrical
potential and a charged substance moves down its
gradient.
e. Presence of Active and Passive Transport Systems, and
Pinocytosis.
Proteins act as transporters that pick up a substance on
one side of the membrane and shuttle it through to the
other side where it is released.
These transporters (carriers) are very selective and
control the transport of specific substances.
Fig 3.3 part 4
3. Membranes are involved in enzyme controlled reactions.
Enzymes (organic catalysts) that alter rate of reaction, are present in
membranes.
Examples:
a. Digestive enzymes in small intestine epithelium.
b. Enzymes involved in electron transfer in mitochondria.
Fig 3.3 part 3
4. Membranes contain binding sites (receptors) for certain
chemicals.
Example: hormones, neurotransmitter, a nutrient.
Fig 3.3 part 6
5. Cytoskeleton anchor (linker)
Anchors cell filaments and tubules of cytoskeleton inside cell to
membrane to aid in stability, shape, or movement.
Physiology 7
PhysiologyStudentsNotes1
22
Cell Organelles and Cell Organization
Chapter 3
see fig. 3.1, p.60
Introduction
All the structures within the cell boundaries are called organelles.
They are all limited by or consist of a membrane. Each has a
characteristic shape and specific function. They are dependent on
each other for cell processes just as the organ systems of the human
body must function together for survival.
Cell Organelles
Nucleus Fig. 3.25 p.84
Control center of the cell.
Contains DNA = heredity blueprints or the genome. We will discuss
DNA and heredity later.
Functions:
1. Contains the information for the synthesis of protein (gene
expression). Fig 3.27 p85 Proteins create structure and functions of the
cell. Ex: contractile proteins, enzymes
2. Controls the cells ability to reproduce (divide).
3. Contains nucleoli- rRNA and ribosomes are manufactured here.
Ribosomes are important structures for protein synthesis.
Endoplasmic Reticulum (ER) Fig. 3.20. p.78
An extensive system of membrane channels (cisterns) that are found
throughout the cell. ER is continuous with the nuclear envelope and
extends throughout the cytoplasm.
Functions:
1. Rough ER primary function is in protein synthesis. Membranes are
studded with ribosomes (appear rough in EM pictures).
Physiology 7
PhysiologyStudentsNotes1
23
2. Smooth ER (without ribosomes) is a site for synthesis of lipids,
steroids (a type of lipid), and carbohydrate, as well as a site to detoxify
chemicals. Via enzymes.
3. ER provides an internal transport system for the cell to process and
sort manufactured molecules and then move them where they are
needed.
Ribosomes Fig. 3.19 p.78
A 2 subunit structure, one large, one small manufactured in the
nucleus and move into the cytoplasm to function.
Ribosomes may be found free in the cytoplasm, mitochondria, or
associated with the wall of ER.
Functions:
1. Is an organelle directly involved in protein synthesis (making of
protein).
2. Rough ER produces protein to be used outside of the cell or in cell
membrane.
3. Free ribosomes are also found in the cytoplasm not associated with
ER. In this case they synthesize protein to be used inside of the cell.
Golgi complex (apparatus) Fig. 3.21 p.79, fig. 3.22 p.80
A membrane complex that processes, sorts, packages proteins and
lipids into vesicles, especially in secretory cells.
Function:
Organizes the protein that has been produced in the rough ER and lipids
into a membrane-bound package (secretory vesicle) for release to the
outside of the cell. Molecules may be modified before release.
Mitochondria Fig. 3.24 p.83
“Powerhouses of the cell”.
This where a process called cellular respiration takes place. Cellular
respiration is a universal process in all cells = aerobic chemical
process that produces energy.
Function:
Physiology 7
PhysiologyStudentsNotes1
24
1. Mitochondria are the major source of energy for the cell.
2. The energy is produced in the form of ATP and the number of
mitochondria varies with the type of cell.
Cells that are very active or synthesize a lot of protein (e.g. liver, muscle,
kidney tubule cells, brown fat) will have more mitochondria than others.
Note: All mitochondria are of maternal origin (from the cytoplasm of the egg).
Mitochondria contain their own DNA (mtDNA). Fathers only contribute nuclear
DNA to their children. Can use to ID missing persons using a maternal
relatives mtDNA.
Lysosomes fig. 3.23 p 81
Lysosomes contain digestive enzymes (60 or so) and low pH (5).
Nickname = “garbage disposal of cell” capable of digesting large
molecules, making smaller molecules of the larger ones.
Functions
1. Things like heat denature (inactivate) proteins so it is necessary to
recycle of them and replace them with a new one. Lysosomes dispose of
the denatured ones by digestion and return amino acids to the
cytoplasm. A wide variety of molecules can be broken down by the
enzymes found in lysosomes.
Human liver cell recycles half its contents per week.
2. If a cell is injured in some way, lysosomes will digest damaged
organelles. Clean up cellular debris in tissue (autophagy).
3. There are specialized cells in the blood stream called macrophages
and neutrophils. When bacteria infect tissue, these phagocytes will
engulf microorganisms and their lysosomes will digest them.
What can happen if lysosomes don’t work right?
Tay-Sachs disease is an inherited disease of a single faulty lysosome
enzyme called HexA. Causes buildup of a membrane glycolipid in nerve
cells that leads to early death (about 5 years of age).
Physiology 7
PhysiologyStudentsNotes1
25
Autolysis occurs at death due to release of lysosomes. It takes effort to
keep lysosomes intact. This ends the rigor state of death after several
hours as lysosomes dissolve cellular structures.
See table 3.2 p 86 for a quick review of cell parts and function.
Cell Organization
Coordination of Cell Organelles
Examining protein synthesis in a basic way will allow you to see the
coordination of various organelles:
Fig 3.27 p 85
a. Blueprint for protein synthesis is found in DNA of nucleus.
b. mRNA carries message down the ER tunnel to a ribosome
where protein is manufactured.
c. Protein travels through ER to Golgi complex where protein is
packaged and excreted to outside of cell through plasma
membrane.
d. Where does energy come from? Mitochondria that makes
ATP for the entire cell.
Reproduction of Cells
Normal Cell Division
2 types: mitosis and meiosis
1. Mitosis: Somatic Cell Division
The Cell cycle fig. 3.31 p.90
Mitosis Fig 3.33 p 92
The reproduction of most cells takes place in a process known as
mitosis = cell division.
In the process of mitosis, 2 daughter cells are produced that are
genetically identical to the parent cell. Same number and type of
chromosomes,
Physiology 7
PhysiologyStudentsNotes1
26
Mitosis takes place in somatic (general body cells) cells, all body
cells except gametes. The rate is different in for each tissue.
Example: skin cells of epidermis, and lining of gut.
Note: We will not study the stages of cell division in this class.
2. Meiosis- Reproductive Cell Division
Sex cells reproduce differently than a somatic cell cells in a process
known as meiosis.
Comparison of mitosis and meiosis fig. 28.2 p.1015
In meiosis the numbers of chromosomes are halved.
Therefore, sperm and egg carry ½ the number of chromosomes
as seen in the somatic cells of the species. For humans ½ = 23.
However, when egg and sperm unite in fertilization, a zygote
(fertilized egg) is produced and the chromosome number is
restored, 46 in humans.
Cell reproduction Gone Wild (Astray)!
“Cancer”- a homeostatic imbalance. Uncontrolled cell proliferation.
A lack of control of the cell cycle. p 95
Typically the number of cells produced by the body balance the
number of cells that have died or are lost, a homeostatic balance.
These processes are monitored in cells locally are under genetic
control.
Ex: p53 is tumor suppressor gene on chromosome 17. It slows cell
growth and may initiate cell death if the cell DNA is damaged. If this gene
is damaged, a wide variety of cancers may results. It has been referred
to as the ‘guardian angel of the genome’.
Neoplasm- Literally means "new formation" but it generally carries
with it the connotation of non-beneficial formation of a cell mass.
Cells divide without the normal controls.
Cells in a neoplasm have no useful function, but like all other cells
require nutrients for nourishment (at the expense of other cells). Due to
Physiology 7
PhysiologyStudentsNotes1
27
rapid growth, they may out compete other cells in the area. This can lead
to weight loss, organ dysfunction, fatigue, or other symptoms a the level
of the human.
There are 2 major types of neoplasms: benign and malignant.
Benign neoplasms
1. Usually grow slowly.
2. Localized within a fibrous capsule that separates them from
normal tissue.
Show no extreme structural differences from other cells.
Benign neoplasms can cause problems!
Create problems if they put pressure on delicate areas like
the brain.
Or if cause excessive output of chemicals like hormones.
Malignant neoplasm- Differ from benign in that they:
1. Grow rapidly.
2. Usually lack fibrous capsules.
3. Commonly release cells into blood or lymph circulation.
Metastasis= movement from one part of body to another (e.g.
cancer cells in this case). New tumors form where cancer filter out
or deposit.
Malignant neoplasms are the second leading cause of death. (#1 =
heart disease)
The word ‘tumor’ is used commonly but does not tell us much
about the problem. Tumor means swelling or mass.
Terminology of cancer (optional discussion)
Neoplasms are named by adding suffix "oma" (tumor) to name of cell of
origin.
Examples:
Melanoma- cancerous neoplasm of melanocytes. Melanocytes produce
skin pigment melanin.
Osteoma- bone neoplasm.
Lipoma- adipose tissue neoplasm. These cells contain fat or lipid.
Causes of Cancer
Physiology 7
PhysiologyStudentsNotes1
28
Neoplasms are believed to be caused by many agents.
Carcinogens are cancer causing agents. Cigarette tars, UV light, and
many chemicals lead to mutations of cell growth mechanisms. Several
mutations are required. A multi step process.
It seems like everything is carcinogenic these days.
Carcinogens are responsible for about 60-90% of cancers.
Heredity is now being demonstrated to also play a major role in cancer
development. Starts you off with mutations from birth that others might
get through environmental exposure.
Viruses are responsible for about 25%. E.g. papillomavirus, hepatitis B,
herpes simplex type II.
7 danger signals of cancer. From the American Cancer Society
1.
2.
3.
4.
5.
6.
7.
Any unusual bleeding or discharge.
Sore that does not heal.
Any change in normal bowel habits lasting > 3 weeks.
Change in size or color of wart or mole.
Chronic indigestion or difficulty in swallowing. Esophogeal reflux.
Lump or thickening in breast or elsewhere in body.
Persistent hoarseness or cough.
Detection Let’s review 4 techniques:
1. Biopsy- removal of tissue for microscopic exam by needle or surgery
for diagnosis by a pathologist.
2. Imaging- X-ray, Cat scans, MRI scans.
3. Blood markers- PSA(prostatic specific antigen), CA125: used to detect
and monitor ovarian cancer. These are proteins found in the blood that
originates from cancerous tissue. They are readily accessible by
venipuncture.
4. Genetic markers- BRCA genes for breast cancer in females.
Others genes also described for familial colon cancer. More discovered
frequently. Can assess risk early in life.
Treatment options
1. Surgery- surgical removal of a will defined tumor and possibly
regional lymph nodes.
Physiology 7
PhysiologyStudentsNotes1
29
2. Chemotherapy- the chance to selectively damage neoplasm to a
greater degree than normal tissues by administering cytotoxic drugs.
Usually a multiple drug treatment by IV therapy.
3. Radiation therapy- focused beam of x-rays to region of tumor to kill
malignant cells.
4. Immune therapy- target malignant cells with an antibody to a unique
marker on tumor cells with adjunct therapy to induced a vigorous
immune response (e.g. IL2).
Other terms
Oncology- the study of tumors
Oncologist- a physician that specializes in diagnosis and treatment of
tumors.
Physiology 7
PhysiologyStudentsNotes1
30
Chemical Organization
Chapter 2
Basic Chemistry Review
Discussion starts on p 27 of text.
When we take a look at living things or living matter, we know that,
like nonliving matter, it is composed of atoms.
Atoms
These extremely small particles are the smallest unit of chemical
division to retain the properties and characteristics of an element.
See periodic table of elements appendix B1
Ex: Hydrogen atom = 10-8 cm in diameter or 0.1 nm.
If and element is broken down by losing some subatomic particles,
further it will change chemical characteristics.
There are dozens of types of subatomic particles, but we will study
only the 3 that are involved in chemical reactions of molecules.
Fig 2.1 p 28
The subatomic particles are the proton, neutron, and electron.
These 3 particles interact to form atoms.
Nucleus of the Atom
The core of the atom = nucleus. The nucleus contains the mass of
the atom.
Within the nucleus are one or more of two type of subatomic
particles.
1. Proton (p+)
1. A positively (+) charged subatomic particle.
2. # of protons in an atom determines its chemical
characteristics and atomic number.
On earth we see naturally occurring atoms made of 1-92 protons
per atom. Synthetic elements have been made by humans.
Physiology 7
PhysiologyStudentsNotes1
31
3. Each of the atoms having various unique properties are
called elements. Fig. 2.2 p.29
Element
A substance composed of atoms that are the same type.
92 natural + 19 or more created by scientists.
Example of elements:
H = 1 proton
C = 6 protons
O = 8 protons
# of protons of an atom = atomic number.
2. Neutron (n0)
The other subatomic particle found in the nucleus of an atom is
the neutron.
It has no (0) charge at all. But the mass = to that of a proton.
1. # of protons + # neutrons of atom = atomic weight
Example:
carbon MW = 6p + 6n = 12
sodium MW = 11p + 12n = 23
2. Atomic weight is approximate since almost all of the mass of an
atom is concentrated in the nucleus.
a. Only a very small portion of mass is found outside the
nucleus.
c. Atomic weight on a periodic table also reflects the
existence of isotopes of that element that contain variable
numbers of neutrons.
Example: carbon = 12.01 So, there are rare isotopes with
more than 6 neutrons. Heavy isotopes tend to be unstable
and degrade over time to more stable configurations.
Note: Some isotopes are useful in medicine to aid in
imaging scans of body systems, however they may be
dangerous to handle because of their radioactive
properties as they degrade.
Physiology 7
PhysiologyStudentsNotes1
32
d. Remember, neutrons do not change the chemical
reactivity of an atom. So, you can have atoms of the same
element with different molecular weights. But the number
of protons must remain constant for the atom to retain its
elemental qualities.
e.
-
Electrons (e )
A third type of subatomic particles exists outside of the nucleus, in
what has been described as a type of cloud are smaller electrons.
Electrons are negative (-) in charge.
The negative charge is sufficient to balance the positive charge of a
proton.
Therefore, if an atom has = number of protons and electrons it is said to
be electrically neutral (0 charge) or a net charge of 0.
If atom contains more electrons than protons or vice versa, it will
have a net charge.
Such an atom is called an ion.
Example: Na+ has 11p and 10e
Cl- has 17p and 18e
Ca+2 has 20p and 18e
Note: Ions are very important in explaining physiologic functions,
especially in muscle and neuron activity.
In comparison to the other subatomic particles mentioned, electrons
have almost no mass.
Example: about one ounce of your body weight = electrons, rest is
protons and neutrons.
Electron = 1/1,840 the mass of a proton or neutron.
Unit of measure of mass = daltons
proton = 1.007, neutron = 1.008, electron = 0.0005
Molecule
Physiology 7
PhysiologyStudentsNotes1
33
We know that atoms combine to form molecules. Molecules provide
for much of the wide variety of characteristics of cells and their
function.
2 or more atoms held together by some kind of chemical bond =
molecule
Introduction to chemical bonds
Electron interactions are the basis of all chemical reactions.
Electrons occupy a shell that will hold a maximum # of electrons.
When the shells are completely filled, they are very stable and
tend not to react with other atoms.
Example: shell #1 = 2, #2 = 8, #3 = 18, #4 = 18 fig 2.2 p 29
To achieve stability an atom tends to empty out or fill up their outer
shell, which ever is more favorable.
Example:
1. Na (AT=11) wants to give up 1 electron, Cl (AT=17) wants to gain 1
electron. So, these 2 react together.
2. He (AT=2) is called inert (won’t readily react with other elements), as
its outer shell is filled.
3. One major factor in predicting the chances of a chemical
reaction occurring between molecules or atoms may be
anticipated based on electronic configurations in these shells.
Chemical bonds p 31 3 types will be discussed:
1. Ionic bonds
Fig. 2.4 p. 31
1. Atoms held together due to their net charges.
2. Formed between strong electron donors (Ex: Na) and strong electron
acceptors (Ex: Cl).
3. Ions form readily in water solutions. Water interferes with the
attraction between ions. Water is a polar molecule with positive and
negative regions.
4. Most ionic bonds in the human body are found in bones and teeth.
2. Covalent bonds Fig. 2.5 p. 33
1. Atoms held together by sharing pairs of electrons.
Physiology 7
PhysiologyStudentsNotes1
34
2. Usually 1, 2, or 3 pairs, noted as a single, double, or triple
bond.
3. Electrons spend time around both bonded atoms in an
attempt to complete their outer electron shells.
4. These are strong bonds that are present in all the
macromolecules and water molecules in our cells.
5. Some molecules are polar to some degree and some are
nonpolar.
a. Polar means that the electrons are shared but spend
more time around one atom than another because on
atom pulls harder than the other on the electrons.
b. A regional negative charge develops on the atom that
pulls the hardest and a positive charge develops on the
atom that is weaker.
Example: water H2O Fig 2.6 p 24 This makes water an excellent
solvent for physiologic fluids.
c. Nonpolar molecules have their electrons distributed
evenly around its atoms and no regional charges form.
3. Hydrogen bonds fig. 2.6 and 7 p 34,
1. Weak bonds where 2 atoms, usually oxygen or nitrogen on
one molecule, associate with hydrogen on another molecule.
2. These bonds do not form a molecule (only 5% as strong as
covalent) but serve as weak links between molecules.
3. They stabilize the structure of many large biomolecules when
many hydrogen bonds are formed as the molecule folds.
Note: These bonds are important to DNA and protein
structure and function.
The bonds act similar to a zipper in these large molecules
with long repeating structures that can hydrogen bond with
each other. 2.24 DNA p. 53
4. H2O molecules can form hydrogen bonds with itself and
other polar molecules.
Physiology 7
PhysiologyStudentsNotes1
35
Atoms of a molecule may be the same. Examples: H2, O2 or
different, H2O, NaCl.
Compound
Atoms will also combine to form compounds.
Molecules are made of 2 or more different kinds of atoms in definite
proportions.
Is H2 or O2 a compound? No.
H2O? NaCl? Yes.
Radical table 2.5 p 42
A distinctive side chain that gives a biomolecule its individual identity.
Called an R group or functional group.
Chemical bonds and Energy Storage
p 31 (chemical bonds), p 54-55 (ATP) p907-8 (anabolism catabolism and ATP)
Molecules and compounds are held together by chemical bonds.
It takes energy to form bonds and a lot of the energy is stored in this
bond as potential energy.
When bonds are broken, this potential energy is released.
Example: ATP is the main energy source in living cells.
It releases and transfers energy from high energy phosphate bonds
to other biomolecules to do work in a cell.
ATP
ADP + Phosphate + Energy
p 55
When you eat sugar, bonds in the sugar are released providing
energy. Fig 25.1 p908
Energy stored in a chemical compound is measured in terms of
calories (lower case c). These are not the same as dietary calories.
The relationship is: 1 dietary Calorie (Cal) or kilocalorie = 1000
chemical calories.
Note upper case C in dietary calorie designation.
Physiology 7
PhysiologyStudentsNotes1
36
Food Energy
In terms of food energy, the food we eat has the following chemical
equivalents:
In chemical calories:
Carbohydrates
= 4000 calories per gram
Proteins
= about same as carbohydrates.
Fats
= 9000 calories/gram
The Composition of the Cell
Important Elements table 2.1 p.28
Of 100 or so elements we know of, 4 elements makeup over 95% of
the body.
These 4 elements are:
C
H
O
N
Carbon
Hydrogen
Oxygen
Nitrogen
18%
10%
65%
3%
These 4 = 96%
Other important elements include (each <2%):
P
Phosphorus
S
Sulfur
These 2 plus 4 above account for 99%
Mg Magnesium
Ca Calcium
Na Sodium
K
Potassium
(mgcanak)
Fe
I
Physiology 7
You can remember these by ‘mechanic’
Iron
Iodine
PhysiologyStudentsNotes1
37
Cl
Chlorine
6 of these elements, CHNOPS will combine in many ways to form
most of the molecules found in living systems.
Important Molecules of Living Systems or Biomolecules
Only a few different kinds of molecules are found in large quantities
in living systems.
Biomolecule
% of body weight
male
female
Water- H2O
60%
62
59
Protein (amino acids)
17%
18
15
C,H,O,N,S
(primarily muscle difference between sexes)
Lipids (fats) C,H,O
17%
14
20
Carbohydrates (sugars)
1%
1
1
C,H,O
Other
5%
5
5
(nucleic acids C,H,O,N,P + certain radicals, minerals, ions)
Total
100%
Important Molecules of Living Systems
Let’s take a closer look at these important biomolecules:
Water p 38-39
Water is the most abundant substance in living systems even though
it is inorganic in origin. It comprises from 60% in rbcs to 92% in
plasma. Lean adult human bodies are 55-60% water.
Its most important function is that of solvent of life’s chemicals.
1. Solvent function of water.
Fig 2.11 p 38
Water is the solvent of our bodies. Solvent = aid dissolving medium.
The reason it is such a good solvent is that it is a polar molecule.
Physiology 7
PhysiologyStudentsNotes1
38
The term "polar" means that one side of the molecule is slightly
positively charged (hydrogen) and the other side is slightly
negatively charged (oxygen).
In the case of water it looks like this:
H2O
See drawing of chemical structure of water showing regional polar
charges: fig. 2.6 and 7 p.34.
The reason for the unequal distribution of charge is that the 2 H atoms
share their electrons with the O atom in the formation of the bond
(covalent).
However, the O keeps the hydrogen electrons more of the time than the
hydrogens have them, making the oxygen side slightly negative and the
hydrogen side slightly positive.
Water will dissolve NaCl because the positively charged sodium ion
(Na+) will be attracted to the O side (negatively charged) of a water
molecule, and the Cl- ion will be attracted to the H side (positively
charged).
Water has other important functions besides being a solvent:
2. Water is the body’s medium for transport.
Fluids are pumped or otherwise distributed throughout the body to
transport nutrients and wastes.
3. Helps maintain cells at a constant temperature.
Water is a good retainer of heat. Called ‘high heat capacity’.
It is difficult to change the temperature of water (due to polar nature).
In other words, it absorbs heat with modest change in temperature.
This helps maintain homeostasis of body temperature.
Much heat can be removed by sweating since water contains energy and
it is dissipated as sweat evaporates.
4. Participates in chemical reactions.
Physiology 7
PhysiologyStudentsNotes1
Fig 2.15 p 44
39
Hydrolysis (breakdown) and dehydration synthesis (join smaller
molecules) of biomolecules.
5. Serves as the body’s lubricant.
Examples: Mucous and other lubricating fluids that lubes chest and
abdomen, joints, moistens foods.
Electrolytes
Within the water of the body we will find ions collectively known as
electrolytes.
Substances that can dissociate into ions (electrically charged atoms)
are electrolytes.
1. + charged ions = cations
As they are attracted to a negatively charge pole (cathode).
Note the ‘t’ in cation can viewed as ‘+’ sign.
2. - charged ions = anions
As they are attracted to a positively charged pole (anode).
Main electrolytes of the body:
Cations
Na +
K+
Ca + +
Mg + +
Anions
Cl HPO4-SO4-- sulfate
HCO3 - bicarbonate
Electrolytes are important in: p 997
1. Osmotic gradients. Example: Na+, K2. Influence enzyme activity. Examples: Mg++
Physiology 7
PhysiologyStudentsNotes1
40
3. Helps maintain a constant pH of about 7.4 for normal cell function.
Components of buffer acid-base systems. Example: phosphates,
bicarbonate.
4. Carry electrical current and establish membrane potentials.
Necessary for muscle and nerve activity, esp. Na+, K+, Ca++.
fig 3.4 p 64
Will discuss this in muscular and nervous physiology chapters.
pH Scale
fig. 2.13 p.41
Scale: 1-14
7 = neutral, > 7 = basic, <7 = acid.
pH 7 means there is 1 x 10-7 [H+] in solution.
Note: the negative exponent is changed to a positive number in the pH
scale.
pH of fluids in the body can vary by function.
Examples: table 2.4 p. 41
Blood pH must be stable between 7.35 to 7.45 or cellular functions
cannot function properly. Death will occur if pH is not restored within
minutes.
Maintaining pH: buffer systems
Weak acid/base + strong acid/base are components of a buffer
system.
Buffers maintain pH in close limits in the presence of strong acids or
bases. Strong acids and bases can contribute H+ or OH- that can
change pH dramatically if not removed. Weak acids and bases acid as
chemical sponges to remove this ions.
See chemical equations for carbonic acid-bicarbonate buffer system. p. 41.
To remove excess of H+, the weak base bicarbonate removes H+.
H2CO3
H+ + HCO3bicarbonate acts as a weak base
Physiology 7
H2O + CO2
PhysiologyStudentsNotes1
41
To increase H+, carbonic acid, a weak acid, dissociates to provide
H+.
H+ + HCO3H2CO3
carbonic acid acts as a weak acid
Example: When a patient having a heart attack comes to the ER and
their pH in 7.0, what buffer is given?
Bicarbonate to remove the H+ and move the pH toward 7.4.
Physiology 7
PhysiologyStudentsNotes1
42
Carbohydrates
Chapter 2
p 43-4
Carbohydrates are compounds made of C, H, O.
see fig. 2.14 for example
structure
Close to the ratio of 1:2:1, or CH2O.
Therefore, the term: carbo (C) hydrate = (H2O) or ‘watered carbon’
Examples: sugars and starches (animal starch = glycogen, plant starch =
cellulose).
Represents about 2-3 % body weight.
Mainly used for energy in humans but can be structural as in DNA,
RNA.
Sugars are formed by photosynthesis. We cannot make them
ourselves, so must consume in diet.
Note: Cellulose is the most abundant organic substance on earth.
It is the primary structural component of plant cell walls.
Humans lack the enzymes to digest cellulose but use it to help digest other
food as dietary fiber.
Carbohydrates have 3 major properties:
1. Have a high caloric value and principal energy source for most living
systems.
2. Are the basic materials from which many other types of molecules are
made.
3. They are soluble in water (except polysaccharides).
There are 3 recognizable forms of carbohydrates:
see table 2.6 p. 43
Monosaccharides, Disaccharides, Polysaccharides.
Mono = 1,
Di = 2,
Poly = many;
saccharide = sugar.
1. Monosaccharides
1. A monomer, the basic building block. 3-7 carbons, usually 5 or 6.
Physiology 7
PhysiologyStudentsNotes1
43
2. Sometimes called "single sugars" a term that includes both monoand di- saccharides
Example: glucose (main energy molecule), (deoxy)ribose, fructose,
galactose (in milk).
2. Disaccharides- "2 sugars". 2 sugar molecules bonded
together.
1. Formed by dehydration synthesis reaction between two
monosccharides. Fig 2.15 p 44
2. Sucrose C12H22O11 Ratio is not quite 1:2:1 because a water
molecule was removed.
Examples:
a. Maltose- malt sugar (2 glucoses joined)
b. Lactose- milk sugar (glucose plus galactose). Some people are
lactose intolerant.
c. Sucrose- table sugar (glucose plus fructose) sugar most
common in plants.
3. Find disaccharides primarily as intermediates in protein synthesis
or breakdown of other carbohydrates in humans.
3. Polysaccharides- "many sugars".
1. Made of many 10s, 100s, 1000s? of monosaccharides linked
together in long chains that may branch.
2. Not soluble in H2O and not sweet.
3. They makeup a storage form of sugar: Glycogen (repeating
glucose units) in liver and muscle.
4. Polysaccharides also play a structural role: Cellulose in plant
cell walls. Not digestible in humans.
Examples: cellulose and starches (glycogen- animals main storage
form).
DNA and RNA in humans and other organisms. Keeps the based
lined up in a regular pattern.
Lipids (fats)
table 2.7 p. 45 p 45-48
Lipids are most commonly fats, waxes, or oily substances.
Contain C,H,O. Less O than sugar.
Physiology 7
PhysiologyStudentsNotes1
44
2 Major Characteristics of Lipids
1. Are water insoluble or hydrophobic.
a. Are soluble in solvents like ether, alcohol, and chloroform,
nonpolar solvents.
b. Combined with proteins for blood transport to form water soluble
lipoproteins.
2. Have C-H bonds in greater proportion than other organic compounds.
Less O bonds means less polar bonding. means more storage of energy.
More C-H bonds leads to their ability to store more than 2x the
energy than an equivalent amount of carbohydrates or protein.
Fats = 9kcal/g Carbohydrates and Proteins = 4 kcal/g
Therefore, they are important sources of energy.
Lipids are stored in cell mostly as fat.
Lipid is synthesized from sugar.
In storage in skin, lipids insulate and are important to help maintain
body temperature.
They give form to the body and cushion organs.
There are 3 major types of lipids we will discuss:
1. Simple Lipids- includes fats, waxes, and oils. Figure 2.17 p. 46
These are the triglycerides, composed of 3 fatty acids bonded to a
molecule of glycerol.
Triglycerides are the major storage form of fat. Excess food energy ends
up here.
They compose the adipose tissue of the body and are the primary lipids
to metabolize for energy by the body.
2. Phospholipids See figure 2.18 p. 47
A lipid portion and a non-lipid portion attached to a glycerol backbone.
Phospholipids are the main component in cell membranes.
Phospholipids are modified triglycerides with 2 fatty acid chains attached
to a glycerol backbone with a phosphate group (which usually links a
small charged group) in the 3rd position.
Physiology 7
PhysiologyStudentsNotes1
45
Lecithin is a good example.
3. Steroids- sterol and steroids. See figure 2.19 p. 48
Steroid structure differs considerably from the triglycerides but they are
nonpolar, fat soluble molecules.
They have 4 rings of carbon atoms.
Examples: cholesterol, sex hormones, cortisol, bile salts, vitamin D.
Cholesterol can contribute to fatty build-up in atherosclerosis but also
serves as the starting material for synthesis of other steroids.
(We will not discuss eicosanoids or other lipids)
Emulsification of Fats
(this topic not discussed in Chapter 2 Tortora)
In order for the body to digest fats it must find a way to make them
soluble.
Bile salts
Which are made in the liver as cholesterol derivatives have this
responsibility.
They work the same way that detergents do to get grease off of
dishes, clothing, etc.
It’s important for us to look at how a detergents works.
How Detergents Work
Lipids in an aqueous solution will go to the top of the water as a film.
Note: Detergents are lipid salts (soap), so have a polar end.
The situation looks something like this:
Draw figure showing lipid layer on top of water in a beaker with tails up,
charged head down.
Draw an individual phospholipid molecule showing the 2 tails (no charge)
and charged head.
Fig 2.18 p.47 shows a phospholipid with similar structure.
A detergent molecule looks like this:
Physiology 7
PhysiologyStudentsNotes1
46
Head Charged (+/-) CH2-CH2-CH2-CH2-CH2....CH3
Hydrocarbon Chain
The head end is charged meaning it is soluble in water (water is a
polar substance and charged molecules, ions, or parts of molecules
will be soluble in it).
The long hydrocarbon chain that forms the tail is not charged and will
not be soluble and water.
However, when detergents are added to lipids in water, the detergent
molecules will react with a lipid molecules to form microscopic
droplets. This is how lipids are made soluble.
Draw a micelle first with the charged heads out and tails inward forming
a sphere.
Now we can add some nonpolar (non charged) fats.
Draw figure showing fat molecules in center of radiating pattern of
detergent molecules with detergent polar heads facing outward
associating with water and tails facing inward associating with fats.
The lipids are protected inside the coating of detergent molecules.
Like dissolves like, so hydrophobic tails go together and polar heads
and water go together.
The fat droplets are emulsified and become soluble with water.
This allows fats to be absorbed and digested in the body. They are
transported in the plasma in this type of structure. Micelles are about 40600 um in diameter. Fig 25.13 p. 920
Review Types of Lipids
Physiology 7
PhysiologyStudentsNotes1
47
1. Simple lipids = triglycerides.
Triglycerides are composed of glycerol bound with 3 fatty acids.
This happens as follows:
Figure 2.17 p. 46. Or,
Draw diagram of glycerol combining with three fatty acids by dehydration
synthesis forming a triglyceride.
Glycerol
+
3 Fatty Acids
=
triglyceride
A fatty acid may be saturated or unsaturated.
1. Saturated
Means every carbon in the hydrocarbon tail has its full complement
of hydrogens.
In other words, all carbons are joined by single bonds as follows:
Fig. 2.17 p.46
Example: animal fats, palm oil, coconut oil.
2. Unsaturated fatty acid
Has doubled (2 pairs electrons shared) or triple bonds (3 pairs
electrons shared) between 2 or more of the carbons in a chain.
In other words, it doesn't have as many hydrogens as is possible or
it could have.
Polyunsaturates contain more than one double bond.
Fig. 2.17 p.46
Examples: corn, safflower, or canola oil.
Saturated fats have a higher energy content (more calories) than
unsaturated fats.
They are also more solid at the given temperature.
Most animal fats are saturated while most vegetable fats are
unsaturated.
Saturated fats and atherosclerosis are linked in diet studies. This
leads to arteriosclerosis. In advanced cases, a heart attack will
occur.
2. Phospholipids
Physiology 7
PhysiologyStudentsNotes1
48
A lipid portion and non-lipid portion.
There is a slight modification of triglycerides to form phospholipids:
1 fatty acid is replaced by a phosphate group with a small charged
group.
Fig. 2.18 p. 47
Example: lecithin
3. Steroids
1. Steroids are nonpolar, fat soluble molecules, that have 4 rings
of carbon atoms that are derived from cholesterol.
2. Cholesterol can be synthesized by the liver or received from
your diet.
3. Important derivatives of it included the sex hormones: estrogen,
progesterone, testosterone.
4. Cholesterol has definitely been implicated in one form of heart
disease known as atherosclerosis where it clumps together in
blood vessels to form crystals and is deposited there.
The cholesterol crystals block the flow of blood.
Fig. 2.19 p 48
Optional Material p 920-1
HDL- high-density lipoprotein. 50% protein, 37% triglycerides, 13%
cholesterol.
Considered good because it lowers cholesterol by soaking up cholesterol
in the blood.
Exercise can increase this beneficial form.
LDL- low density lipoprotein. 25% protein, 20% triglycerides, 55%
cholesterol
Considered bad because it increases circulating cholesterol that can
cause deposits.
Increased by high fat diet and little or no exercise.
High levels of serum cholesterol (>150mg/dl) are associated with
increased risk of coronary disease.
Physiology 7
PhysiologyStudentsNotes1
49
For those with very high cholesterol (>200 mg/dl) that diet and exercise
don’t correct can take drugs (e.g. Zocor, Lipitor blocks synthesis in liver
or drugs that block adsorption in the GI tract).
Physiology 7
PhysiologyStudentsNotes1
50
Proteins
Chapter 2
p 48-52
Proteins are very large molecules composed of long chains of
nitrogen containing molecules known as amino acids.
They have a large range of function, both structural and physiological
roles.
Made from these elements: C, H, O, N, and S.
The major proteins functions include:
table 2.8 p. 48
1. Structure
They can be structural elements within cells.
Examples: Collagen is a protein in bone and other C.T.
Keratin is found in skin hair and nails.
Silk, wool, horns, and antlers are made from structural
proteins.
2. Regulatory (hormones)
Chemical messengers in the body that regulates various
physiological processes, and, control growth and development.
Examples: Insulin regulates blood glucose level by controlling entry into
cells and is a protein hormone.
3. Contractile
Allows shortening of muscle tissue that produces movement.
Examples: Myosin and actin form contractile filaments that pull against
each other and shorten the muscle.
4. Immunological
Provides a specific response to protect the body against foreign
substances and invading pathogens.
Examples: Antibodies and interleukins (IL2, TNF).
5. Transport
Carries vital substances throughout the body.
Physiology 7
PhysiologyStudentsNotes1
51
Example: Hemoglobin carries 02 from the lungs to the body.
Catalytic (enzymes) Fig. 2.23 p.52
Enzymes are catalysts in cells. They speed up chemical reactions.
These reactions can build up or breakdown biological compounds.
Lock and key analogy: one enzyme for each reaction.
Speeds up reaction 108 to 1010 times more rapid than reaction
without enzymes.
All enzymes are proteins, but not all proteins are enzymes.
6.
Examples: named with suffix –ase.
Amylase breaks down starch.
Lipase breaks down lipids.
Lactase breaks down lactose.
Amino Acids and Polypeptides
Proteins are made of amino acids. There are 20 amino acids used
to make proteins. Fig 2.20 p 49
Amino acids are strung together in polymers to form individual types
of proteins.
Polymers are larger molecules composed of many repeating molecular
subunits.
Example: Insulin is composed of 51 amino acids strung together.
You can see that with 20 different amino acids, there are many different
types of combinations possible.
The sequence in which the amino acids are arranged in the
polypeptide chains(protein) determines the biological characteristics
of the protein molecule.
Even one small variation in this sequence can cause disaster.
One change (substitution) of an amino acid in a protein can alter the
shape of the protein and render it non-functional.
Example: Sickle cell disease is the mutation of a hemoglobin gene
at one amino acid.
Hemoglobin has 574 amino acids in four chains
(2 alpha chains (141 a.a.), 2 beta chains (146a.a.)). Fig 19.4 p 640
Physiology 7
PhysiologyStudentsNotes1
52
Valine (hydrophilic) replaces glutamic acid (hydrophobic) at
position 6 of the beta chain that causes the hemoglobin to change
shape under low oxygen levels to create sickle-cell shaped red
blood cells. Fig 19.14 p 654
Cells get stuck in micro-circulation causing hypoxia and tissue
damage. Can be deadly in the homozygous state (2 copies of the
sickle gene, that is one inherited from each parent).
The spleen can become quite enlarged.
Amino Acid Structure:
figure 2.20 p. 49
Amino acids, since they make up proteins, are composed of the
same elements as protein: C,H,O, as well as N.
Some amino acids (cysteine, methionine) will contain S that will bond
with other S containing amino acids to create covalent bonds to reinforce
the shape of the protein, as we will review later.
Every amino acids contains an amino group (-NH2) and a carboxyl
group (-COOH) bonded to a carbon atom:
figure 2.20.
R
|
H2N – C- C -OH
| ||
H O
Amino group – C – Carboxyl group
This is the basic structure of the molecule. It is the same in all amino
acids.
R (side chain)
A group of atoms that acts as a single functional unit. The R group
gives the amino acids its particular chemical behavior.
Examples: hydrogen bonding, sulfhydryl bonding (S-S), polar and
nonpolar affinities. Remember what happened to hemoglobin with one
change.
Physiology 7
PhysiologyStudentsNotes1
53
Examples: fig 2.20 p 49
When R = H
When R = CH3
Glycine (gly)
Alanine (ala)
When R = CH2-OH Serine (ser)
When R = CH2-SH
H
|
H2N-C-C-OH
| ||
H O
H
HCH
|
H2N-C-C-OH
| ||
H O
OH
|
CH2
|
H2N-C-C-OH
| ||
HO
Cysteine (cys)
SH
|
CH2
|
H2N-C-C-OH
| ||
HO
Since proteins are made of chains of amino acids, let's look at how
amino acids are bound together to make proteins.
The amino "head" of the molecule can be linked to the carboxyl "tail"
of another by the removal of a water molecule. This forms a covalent
bond call a peptide bond. See figure 2.21 p. 49
This is called dehydration synthesis.
Physiology 7
PhysiologyStudentsNotes1
54
When several of these linkages form, combining several amino acids, the
molecule is called a polypeptide.
Polypeptides are assembled in the ribosome, linking the head of one
amino acid to the tail of another, like a line of box cars.
The sequence of the box cars (amino acids) is determined by information
from the nucleus of the cell.
As the amino acids produce a linear chain on the ribosome the
primary structure of the protein is determined.
see figure 2.22 p. 51
The primary structure is the unique sequence of amino acids making up
a protein.
It will ultimately determine the shape and function of the protein.
(Remember function changes as the shape changes, for better or worse)
3 other levels of protein organization are important to their function:
Secondary structure
The protein, commonly assumes an alpha helix (clockwise spirals similar
to a phone cord) or a pleated sheet repeating pattern.
Tertiary structure
This level of protein structure describes the 3D shape of the protein
molecule.
It is determined by the side chain (R group) interactions that form
hydrogen bonds, ionic bonds, covalent bonds, hydrophobic interactions.
This level determines the proteins primary function.
It is similar to the irritating secondary winding of the phone cord that
occurs with use.
Quaternary structure
Some proteins contain more than 1 polypeptide chain.
This level describes the bonding of individual polypeptide chains relative
to each other. They are held in place by bonds as mentioned under
tertiary structure.
Physiology 7
PhysiologyStudentsNotes1
55
Example: Hemoglobin consists of 2 alpha chains and 2 beta chains to
form one functional protein.
Small changes in temperature, pH, or electrolyte concentrations in the
body can cause protein structures to unravel and lose their characteristic
shape.
This process is called denaturation.
This will affect the ability of the protein to perform its function.
Example: cooking an egg, lowering the pH of milk, sunburn producing
curdled or denatured proteins
Physiology 7
PhysiologyStudentsNotes1
56
Nucleic Acids
Chapter 2 p 52
Note- you should receive a handout copy of the genetic code in lecture
Nucleic acids include 2 types:
1. Deoxyribonucleic acid or DNA
Forms the inherited genetic information (material) inside the nucleus
each cell, your DNA.
DNA = blueprints (genome) for the control of cellular activity.
2. Ribonucleic acid or RNA
RNA relays instructions from DNA to the cell to make amino acids into
proteins.
Control by Nucleic Acids
DNA along with certain proteins (histones) make up chromosomes
that contain the blueprint (genome) of life.
Humans have 46 (2x23) chromosomes, 23 from each parent.
There are about 30-38K genes in a human , so about
1500/chromosome.
The genetic information (genome) in chromosomes (DNA) has to get
out of the nucleus and into the cytoplasm to control cell activities.
A certain type of RNA is responsible for this: messenger RNA or mRNA.
mRNA carries the genetic message from DNA out of the nucleus to the
ribosome in the cytoplasm.
The end result being that the genetic message is taken from the mRNA
and translated into a sequence of amino acids to make proteins.
This is called the Dogma of Life.
DNA
mRNA
Chemistry of Nucleic Acids
Physiology 7
protein
fig 2.24 p. 53
PhysiologyStudentsNotes1
57
In order to understand how this works, it is necessary to take a
closer look at nucleic acid chemistry.
The primary elements found in nucleic acids are C,H,O,N,P.
The basic unit of a nucleic acid = nucleotide.
DNA is made of thousands of nucleotide subunits strung together.
DNA molecules are huge, the largest molecules in the cell.
Molecular weight = 1 million to several billion. Up to 100,000 times the
size of most proteins.
Each nucleotide is made of 3 components:
figure 2.25 p. 54.
1. Phosphate group. PO432. Sugar- deoxyribose in DNA, ribose in RNA.
3. Base (nitrogenous base). 2 sizes: double ring purine, single ring
pyrimidine.
Note: The base is the only chemical structure that differs from one
nucleotide to another. The sugar and phosphate act as repeating
structures in DNA and RNA to keep the bases exactly lined up
opposite with each other. The bases determine the information in
the genetic code.
There are only 4 different kinds of bases in DNA:
Adenine (A)
Guanine (G)
Cytosine (C)
Thymine (T)
The 4 bases of RNA are:
Adenine (A)
Physiology 7
Guanine (G)
Cytosine (C)
Uracil (U)
Note: only uracil differs from DNA bases
PhysiologyStudentsNotes1
58
The organization of the components of a nucleotide is as follows:
where
phosphate = P sugar = S base = B
P
\
S-B = 1 nucleotide
Nucleotides join together to form a strand of DNA like this:
P
\
S-B
= 1 nucleotide
S-B
= 1 nucleotide
S-B
/
= 1 nucleotide
S-B
= 1 nucleotide
/
P
\
= strand of nucleotides
/
P
\
P
\
Further simplification:
1 strand of nucleotide looks like 1/2 ladder, where: rungs = base,
side of ladder = sugar + phosphate
|-B
|-B
|-B
|-B
|-B
Physiology 7
PhysiologyStudentsNotes1
59
In 1952, 2 men, Watson (American) and Crick (British) formulated
current model of molecular of DNA.
They postulated that DNA is made up of 2 strands of nucleotides
wrapped around each other.
Published in 1952, Nobel prize in 1962.
There work has been confirmed by decades of research.
The overall shape is a double helix (double coil), with the bases of
each strand sticking inwards from the backbone and bonding with
each other. see fig. 2.24 p.53
The 2 opposing strands appear bound by a ‘zipper’ of hydrogen bonds
between bases.
DNA double helix has bases projecting inward from opposing twisted
helix strands.
Looks like a twisted ladder. Consists of thousands of nucleotides strung
together. How many are shown here? 1 for each B (base).
See diagram in a 3D helix view, and a 2nd, in a flat, unwound view.
Base Pairing of DNA Nucleotides
Bases = Adenine (A)
Guanine (G)
A will only pair with T: A-T or
T-A
G will only pair with C: G-C or
C-G
Cytosine (C)
Thymine (T)
Note: A and G are larger bases while T and C are smaller bases.
A large base must bind to a small base for the DNA molecule to fit
together correctly.
Physiology 7
PhysiologyStudentsNotes1
60
Therefore, base pairs of DNA strand could look like this:
|-T
|-A
|-C
|-G
|-T
|-A
What are the base pairings for this example?
On an exam if you are given the bases in one strand of DNA you should
be able to determine the nucleotide sequence of the complementary
strand.
The strand of the DNA that contains the genetic information (gene) is
called the "antisense" or “gene” strand.
The strand of DNA complementary to the sense strand is called the
"sense" strand because it is similar to the mRNA sequence. This will
more sense after more discussion.
Base Pairing in RNA Nucleotides
Bases =
Adenine (A)
Guanine (G)
G will only pair with C: G-C or
U will only pair with A: U-A or
Cytosine (C)
Uracil (U)
(uracil replaces thymine)
C-G This is the same as DNA.
A-U U takes the place of T in RNA.
Other Differences Between DNA and RNA
RNA sugar = Ribose
RNA consists of a single strand of nucleotides.
mRNA is smaller, containing 300-3000 nucleotides.
If only single-stranded, what does RNA bases pair with?
RNA may twist upon itself to give a 2 stranded look (tRNA) or will
exist as single-stranded, mRNA.
Physiology 7
PhysiologyStudentsNotes1
61
What does mRNA pair with?
mRNA takes the genetic message from DNA in the nucleus to the site of
protein synthesis at the ribosome. An mRNA molecule represents the
code for one protein.
So, it is created on DNA in the nucleus at the site of a gene coding for a
protein.
And then it pairs with tRNA at the ribosome.
Where are ribosomes?
In the cytoplasm or ER.
mRNA leaves the nucleus through a nuclear pore to enter the cytoplasm
and then to free ribosomes or ER with ribosomes.
Transcription figure 3.28 p. 87
Transcription is the process where the directions found in DNA to
make a protein are transcribed to create an mRNA molecule.
See below a nucleus showing double stranded DNA and mRNA leaving
the nucleus through a nuclear pore. Note the nucleus with sense and
anti-sense DNA strands. Identify the base pairing needed to create the
mRNA. Explain how DNA acts as a template for mRNA.
Nucleus
nuclear pore
nucleus
|-T A-|
|-A T-|
|-C G-|
|-G C-|
|-T A-|
|-A T-|
U-|
A-|
C-|
G-|
U-|
A-|
cytoplasm
DNA
mRNA
antisense sense
Physiology 7
PhysiologyStudentsNotes1
62
The process where genetic information of DNA is used to specify
base sequences of mRNA is called "transcription".
Be prepared to transcribe an mRNA strand from a DNA strand that I will
provide for you.
How does each newly formed somatic cell in your body obtain
genetic information?
Before mitosis, the cell creates a second set of chromosomes in a
process called DNA replication. So, briefly there are 92 copies of the
chromosomes, then one set of 46 goes to each daughter cell as mitosis
procedes.
The Genetic Code
Once the DNA is transcribed into mRNA it travels to the ribosome
and tells ribosome what amino acids to connect together to make
protein (translation).
Translation
The information in mRNA dictates the sequence of amino acids to be
placed in protein molecules.
Example:
Initiator
Terminator
AUG leu ser pro ala tyr
UAA
a.a. - a.a- a.a- a.a.- a.a.- a.a. And so on. a.a
How does DNA code for 1 of 20 specific amino acids in sequence to
make protein?
Through tedious research it has been found that a 3 base sequence in
DNA is transcribed into a 3 base code in mRNA for a particular amino
acid.
So, each group of three bases represents an amino acid in the
building a protein.
The code for a particular amino acid has been termed a "codon".
Physiology 7
PhysiologyStudentsNotes1
63
Example:
DNA (gene)
A
A
A
A
G
A
T
T
T
G
C
A
mRNA
U
U
U
U
C
U
A
A
A
C
G
U
Amino acid
phenylalanine
serine and
lysine
arginine
The bases are analogous to a 4 letter alphabet, and the codons are
analogous to words spelled with 3 letters.
1. There are 64 different codons as follows:
43 = 64, where 4 = the four bases, 3 = 3 bases/codon.
2. So, there are 64 different ways that A,T,G,C can combine to form 3
letter codons.
3. Most (18/20) amino acids have more than 1 codon.
Example:
Valine: There are 4 codons for valine.
GUU
GUC
GUA
GUG
Some amino acids have 6 codons (leucine, serine, arginine).
Most amino acids have between 2-6 codons.
4. When different codons code for the same amino, demonstrating a
redundant or degenerate code.
5. Some codons act as punctuation marks, 1 start, 3 stop codons, that
tell the ribosome when to start and stop and amino acids chain.
The stop codons are also known, less appropriately, as "nonsense"
codons.
Physiology 7
PhysiologyStudentsNotes1
64
Control by Nucleic Acids in Protein Synthesis figure 3.30 p. 89
The synthesis of a protein requires that certain things are present
within the cell:
In Nucleus
1. DNA
2. Free nucleotides floating around that can combine to form mRNA.
In Cytoplasm
1. Ribosomes
2. The 20 various amino acids that will eventually be joined together in
proper sequence to form protein.
3. ATP = energy source (which is also a nucleotide).
4. tRNA = transfer RNA.
tRNA is made in the nucleolus and moves out of the nucleus and
into the cytoplasm through nuclear pores.
Anticodons
tRNA is a small molecule that looks like this:
fig. 3.30 p.89
See the tRNA molecule with one end for attachment of a specific
amino acid, and the other end for the 3 base anticodon that is
complementary to the mRNA codon.
Example: anticodon CGU = alanine a.a. end
The anticodon determines what amino will attach to tRNA.
1. In the presence of ATP, an amino acid is activated and attaches to
tRNA.
2. Only the amino acid represented by the anticodon can attach to the
tRNA.
So, there is an tRNA type for each codon representing an amino acid.
3. Where do amino acids come from?
Your diet. If your diet does not contain all 20 amino acids, this
causes a disease called kwashiorkor. It rarely occurs in developed
Physiology 7
PhysiologyStudentsNotes1
65
areas of the world. Mainly in areas where starchy foods are a
staple of the diet. Meat and milk contain all 20 amino acids.
Now that we know what things must be present in the cell for protein
synthesis, how do they work together?
Sequence of Events for Protein Synthesis
fig 3.28 p 87, 3.30 p 89, text p 88
1. Free nucleotides are attracted to DNA strand where
complementary base pairing occurs.
2. Nucleotides link to form mRNA strand.
Steps 1&2 are the process called Transcription.
3. mRNA separates from DNA and moves out of nucleus to
associate with ribosomes.
Structurally, a ribosome consists of 2 subunits, one about half the size of
the other.
The smaller ribosomal subunit complexes with tRNA, mRNA, and
proteins to initiate reading of the mRNA message.
4. Free amino acids in cytoplasm combine with their respective tRNA
carriers.
5. tRNA anticodon with associated amino acids, base pairs with
mRNA codons at ribosome. The ribosome then moves along the
mRNA strand.
6. Ribosome continues moving along mRNA strand to new codons,
where amino acids are added to a growing polypeptide chain.
tRNA molecules are released as the amino acids are joined by a peptide
bonds.
The next tRNA carrying an amino acid attaches by anticodon to the next
mRNA codon to continue the process.
Steps 3-6 represent the translation process.
Physiology 7
PhysiologyStudentsNotes1
66
7. Polypeptide disconnects from the ribosome and mRNA strand
when a "stop" codon is reached.
One of three codons: UAA, UAG, or UGA.
There are no tRNA that recognize these codons.
These proteins determine the physical and chemical characteristics
of the cell.
They have many functions:
1. Structural: plasma membranes, microtubles, microfilaments,
centrioles, flagella (cilia), mitochondria, etc.
2. Enzymes that run the cell’s metabolism.
3. Others: Hormones, antibodies, contractile elements in
muscle.
Proteins carry out life functions. DNA only contains codes for the
potential for life. Life does not exist without protein.
Physiology 7
PhysiologyStudentsNotes1
67
Review of Protein Synthesis
Chapter 3
Review of the 7 step process of protein synthesis starting with
transcription of DNA to mRNA through the process of translation.
1. Nucleotides to DNA.
Fig 3.28 p 87
Draw nucleus with double stranded DNA showing complementary base pairing
between the sense and anti-sense strands.
Show free nucleotides beginning to base pair with sense strand.
2. mRNA single-strand forms. Fig 3.28 p 87
Draw mRNA molecule along side the sense strand of DNA demonstrating
complementary base pairing between the sense strand and mRNA.
Show free nucleotides in nucleus being attracted to the mRNA transcription
process.
3. mRNA separates and moves to ribosome. Fig 3.28 p 87, fig 3.30-1 p 89
Draw mRNA path as it would move from the nucleus via a nuclear pore to
arrive at a ribosome.
4. Amino acids bind to tRNA. fig 3.30-2,3 p 89
Draw a simple tRNA molecule reacting with an amino acid (valine, anticodon =
CAU) and ATP to form an activated tRNA-amino acid complex.
Show free amino acids floating in the cytoplasm.
5. Translation begins. Fig 3.30-3,4 p 89
Draw 2 ribosomes attached to mRNA, reading codons. Codons sequence:
AUG (start/methionine), UUC (leucine) show tRNA here with ribosome, GUA
(valine), UAC (tyrosine), CGA (arginine), GAG (glutamic acid) show tRNA here
with ribosome, UAA (stop codon).
6. Translation continues as ribosome moves along mRNA strand. Fig
3.30-5 p 89
Draw a peptide forming behind the second ribosome with glutamine tRNA –
arginine-tyrosine, valine, leucine, start/methionine.
Physiology 7
PhysiologyStudentsNotes1
68
7. Stop codon is reached and polypeptide disconnects from
ribosome. Fig 3.30-6 p 89
Demonstrate effect of reaching the stop codon.
This is an amazing process when you think about it.
Protein synthesis progresses at a rate of about 15 amino acids per
second.
Several ribosomes may be attached to the same mRNA forming the
same protein simultaneously.
Humans have DNA to code for about 30K-40K genes.
Some proteins can be modified several ways after translation in the
cell so one gene can code for more than one function.
Every cell of the body contains the same information in the form of
DNA.
Example: A skin cell contains the part of the DNA that tells the skin cell
how to function as well as how a muscle cell is supposed to function.
To put it another way, each cell contains the genetic information
necessary to reproduce a new organism.
This has been demonstrated recently by the cloning of mammals from
somatic cells.
The fact that each cell does not reproduce a whole new organism
shows that there are many other factors besides nucleic acids that
determine what a cell does or does not do. This will be discussed
soon.
The genes of eukaryotes, such as humans, contain stretches of
bases called exons and introns. p. 88
Exons: stretches of DNA that code for protein.
Introns: intervening stretches of DNA that do not code for
protein.
When an mRNA transcript is made, the introns must be removed and the
molecule spliced back together.
Physiology 7
PhysiologyStudentsNotes1
69
Prokaryotes read their genes directly into functional mRNA. In other
words, prokaryotes only have coding sequences.
This creates a problem for cloning human genes into prokaryotes.
Prokaryotes have no cellular machinery to remove introns from
eukaryotic genes.
So, yeasts, plants, and other animals (all eukaryotes) are
becoming popular human gene recipients.
DNA Replication
How does a cell initially receive genetic information?
During cell division (mitosis).
DNA doubles itself by a process known as DNA replication.
This is not a copy but a mirror image replication by complementary
base pairing.
The Human Genome Project is currently mapping out the 3 billion base
nucleotide pairs in the human genome.
Replication takes place as follows:
Make these drawings side by side as we go through lecture.
Make stick figure with DNA backbones and rungs.
Use different color each DNA strand in double helix.
Fig 3.32 p 91
Draw a double helix.
Draw a double helix unwound (ladder-like).
Draw the DNA strands separated.
Draw each strand and show how free nucleotides base pair with
each strand.
Draw 2 new strands of DNA pairing with the existing strands.
Draw 2 new strands coiled up in separate double helix structures.
These 2 chromosomes are identical to the parent chromosome.
In other words the genetic information is the same.
Physiology 7
PhysiologyStudentsNotes1
70
If mistakes are made in the DNA sequence, the cell could die or cause a
problem such as cancer.
Each new chromosome goes to 1 of the new daughter cells formed
during mitosis. Fig 3.33d p92
One theory on aging is chromosomes get shorter due to erosion of
their tips (telomeres).
Each cell division shortens the telomere until it is completely gone and
function is lost.
Mutations
(Not covered in Tortora textbook)
Introduction
A mutation is a mistake at some point in the DNA message. Think of
DNA as a structure that has shape and form. If the structure is
altered, the message is changed, and therefore the protein (s) will
change.
We can view mutations at the molecular level now that we know the
structure of DNA.
Mutation
An alteration in genetic makeup (genotype) of an organism at the
molecular level.
It is an alteration in the base sequence of DNA that gets transcribed into
RNA and then translated into protein.
Such alterations may or may not affect the appearance (phenotype) of
an organism. The mutation can result in an improvement, a weakness, or
no change in the function of the proteins(s).
Mutagens Is an agent that increases likelihood of mutation.
Mutagenic Agents
Examples:
2 types
Radiation
Physiology 7
PhysiologyStudentsNotes1
71
1. Ionizing: High energy x-rays and gamma rays strike molecules
and cause them to ionize. Reactive radicals cause changes at the
molecular level, such as base changes, chromosome breakage.
Examples: x-rays
Use a lead shield for protection of sex organs of patient and
operator.
2. Non-ionizing: UV light from the sun (especially at 260 nm that is
mostly filtered by the ozone layer) cause harmful covalent bonds
between adjacent thymines, forming thymine dimers.
This causes mistakes in transcription and replication.
Example: UV rays- from sun causes thymine dimers in skin cells
and leads to skin cancers. Light repair enzymes act to separate the
dimer into separate thymines.
Humans with xeroderma pigmentosum have genetic defects in
their light repair enzymes and are at great risk of skin cancer.
Chemicals
A long list goes and new ones identified every day.
Examples: mustard gas, phenol, and formaldehyde.
In medicine: base analogs such as AZT used to treat HIV virus to create
base pair substitutions.
Can these mutations be passed onto future generations?
Only if they occur in the germ cells, sperm or egg.
The atomic bomb irradiation in Japan lead to high incidents of
leukemia in offspring.
Spontaneous mutations- "naturally occurring"?
Mutations occur at a slow rate all the time in all organisms.
The normal rate is estimated at once in 10-6 replicated genes.
Or once in 109 replicated base pairs (10-9mutation rate).
An average gene has 103 base pairs.
A mutagen increases this rate by a factor of 10-1000 times.
Are all mutations harmful?
No! That is how evolution takes place.
Diversity provides the raw material for evolution.
Physiology 7
PhysiologyStudentsNotes1
72
Look around the classroom and see all the genetic diversity among your
classmates. Some of us are better adapted to different environments.
Evolution represents a combination of changes in the genotype and
natural selection acting upon it.
As the environment changes, the value of a particular gene will be
increased or decreased.
Types of Mutations
At the molecular level, all mutations are changes in the genetic code
of an organism. In some way, the sequence of bases (A,T,G,C) has
been altered and one or more codons has changed.
Mutagens may cause:
1. Substitutions
Substitutions of an incorrect for a correct nucleotide.
Analogy:
Literally:
say it with g(f)lowers.
CAT
(GUA valine codon)
Becomes: CAG
(GUC valine codon)
2. Inversion
2 nucleotides have been reversed.
Analogy: We put our trust in the untied nations.
Literally: CAT (GUA valine codon)
Becomes: CTA (GAU aspartic acid codon)
Substitutions and inversions are types of point mutations, as they
only alter the message for 1 or maybe 2 amino acids in the
sequence.
3. Deletion
Missing nucleotide in sequence.
Analogy: The Prime Minister spent the weekend in the country shooting
p(h)easants. or,
Delete the letter F from FAT make the sentence meaningless.
THE FAT CAT ATE THE RAT
Physiology 7
PhysiologyStudentsNotes1
73
THE ACT ATA TET HER AT
Remove A in first codon in a three codon sequence
Literally:
CAT
valine
GUA codon
TTA
GCA
leucine arginine
AAU codon CGU codon
Becomes:
CTT
TAG
CA? every codon after this altered.
glutamic acid isoleucine different a.a.
GAA codon AUC codon GU? codon
4. Insertion
Additional nucleotide is added to sequence.
Analogy: The Treasury controls the public monkeys. Or,
Insert the letter C before FAT make the sentence meaningless.
THE FAT CAT ATE THE RAT
THE CFA CTA TAT ETH ERA T
Add G in first codon in three codon sequence
Literally:
CAT
valine
GUA codon
TTA
GCA
leucine arginine
AAU codon CGU codon
Becomes:
CGA
TTT
AGC A every codon after this altered.
alanine lysine
serine
GCU codon AAA codon UCG codon C??
Deletion and insertions are more drastic and are called frame-shift
mutations.
They alter entire amino acid sequence following the mutation, causing a
dysfunctional protein.
They also may lead to the insertion of nonsense (stop) codon
substitutions.
Why are visible mutations so rare?
Most mutations usually affect only 1 member of a pair of alleles.
Alleles represent 1 of 2 or more genes responsible for a certain trait.
Physiology 7
PhysiologyStudentsNotes1
74
Example:
Usually the normal allele exerts its effect more strongly (dominant).
Most mutations are recessive.
Example:
Cystic fibrosis: a disease of a cell membrane protein.
Cc or Cc = Normal membrane function,
cc = faulty Cl- transport protein in membranes.
But the defect is still carried as a recessive trait.
(These recessive traits often have a hidden advantage. CF gene is
protective against Salmonella infection.)
May be expressed in future matings, especially when inbreeding is
common.
Only if a DNA mutations occur in the germ cells (egg or sperm), will
they be passed on to the next generation.
Operon Theory of Gene Control by Nucleic Acids
What controls when protein made or not?
Regulation of protein synthesis is important to the cell’s energy
economy.
The cell can save energy by only making proteins for particular need.
Most genes are constitutive (60-80%), meaning their products are
produced at a constant rate.
These gene products are needed in large amounts for essential
processes common to all cells.
Some genes are conservative, meaning that their product production is
regulated so they are present when needed.
Example: Insulin is made after meals to let glucose enter cells.
According to this theory there are 3 segments (genes) of the DNA
strand involved in the production and control of the production of
proteins.
Physiology 7
PhysiologyStudentsNotes1
75
The 3 segments are the:
Structural gene- the gene(s) segment that codes for the functional
protein.
Operator segment- the short segment of DNA that contains the
operator/promoter complex that acts as attachment site for RNA
polymerase and initiation of transcription.
Regulator gene- codes for repressor protein that binds tightly to operator
site.
Physiology 7
PhysiologyStudentsNotes1
76
Operon
Control Region
Structural gene(s)
DNA
Regulatory
gene
Promoter
Operator
1
2
3
Structural gene(s)
= Repressor protein
A DNA strand with an operon (promoter/operator, structural genes) and
regulator gene. Show inducer protein, repressor protein.
Operon
Combination of the control region and structural gene.
Note: Regulator gene may be near the operon or located somewhere
else on DNA strand.
Operation of the Operon:
In this example, the cell only makes proteins to metabolize lactose when it is
present and needed for cellular metabolism. The cell needs 3 proteins to digest
lactose (1, 2, 3)
When lactose is present in the cell, a small portion is converted to an inducer
substance that can bind to the repressor protein.
It changes the shape of the repressor protein and it releases form the operon
and allows for the transcription of the structural genes needed to metabolize
lactose.
When the inducer is not present, the repressor protein will again bind and
block the structural genes from being transcribed.
This is known as an inducible system of control.
This demonstrates the role of nucleic acids in the control of cell activity.
Physiology 7
PhysiologyStudentsNotes1
77
Recombinant DNA
(cover if time permits) p 90
Recombinants
Organisms that have another organisms gene(s) inserted into its
genome. The organisms takes on the characteristic(s) contained in
the gene(s).
Transgenic
Inserting a gene from one species into another species genome.
Products
There are 2 products that can be useful in the transgenic organism.
1. Genes-: Genes can be manufactured in large numbers so that they
can be inserted in the original species to correct genetic defects.
Example: CF gene can be replaced with a normal gene in a person
born with CF.
2. Protein: Proteins can be harvested that have a wide variety of uses.
Examples: Many modern medicines are made by genetically
modified organisms, usually yeast or bacteria.
Growth hormone (hGH), insulin, clotting factors, interferon (INF),
erythropoietin (EPO), vaccines (HepB)
Other control of cell activity.
Hormonal Control
(Cover if time permits)
Hormones = chemical messengers produced by endocrine glands.
Travel by means of bloodstream, a shotgun approach.
Hormonal control at areas sites:
1. Influence cell membranes.
Example: Influence permeability. Insulin acts to accelerate facilitated
diffusion of glucose into cells.
2. Influence activity of enzymes.
Physiology 7
PhysiologyStudentsNotes1
Fig 18.4 p 593
78
Water soluble hormones typically bind a membrane protein (G –protein)
that will activate a secondary messenger (usually cAMP) inside the cell.
The secondary messenger will activate or inactivate enzymes in the cell.
Examples: Epinephrine binds to liver cells and causes inactivation
of an enzyme needed for glycogen synthesis.
In vitro- in test tube.
In vivo- in living organism.
3. Influence genes.
Fig 18.3 p 592
Lipid soluble hormones enter the cell through the phospholipid
membrane where they bind to receptors that alter gene expression (turn
gene on or off).
The resulting protein (or loss) will have an effect on cellular metabolism.
Example: estradiol, progesterone
Exam 1 Notes
Multiple choice- 50 points
Matching- 10 points
Fill in- 5 points
Essay- 10 points
Physiology 7
PhysiologyStudentsNotes1
79